The exclusion of exclusion in social capital

In this paper we argue that many scholars using the conceptual framework of social capital have largely ignored or minimised two important elements: closure and emergence. First we chart the rise of social capital (section two), then we outline some of the existing criticisms of social capital (section three). In section four, we offer a four-way classification system, based on the recognition of emergence and/or closure, of the most popular and widely utilised definitions of social capital. Such categorisation allows for the analysis of how social capital is understood across academic disciplines and how it has been taken up in the policy making arena. Finally we argue that it is only by conceptualising social capital as having emergent properties and as inherently exclusionary that it becomes theoretically and analytically useful to sociological enquiry.

Developing Wound Moisture Sensors: Opportunities and Challenges for Laser-Induced Graphene-Based Materials

Recent advances in polymer composites have led to new, multifunctional wound dressings that can greatly improve healing processes, but assessing the moisture status of the underlying wound site still requires frequent visual inspection. Moisture is a key mediator in tissue regeneration and it has long been recognised that there is an opportunity for smart systems to provide quantitative information such that dressing selection can be optimised and nursing time prioritised. Composite technologies have a rich history in the development of moisture/humidity sensors but the challenges presented within the clinical context have been considerable. This review aims to train a spotlight on existing barriers and highlight how laser-induced graphene could lead to emerging material design strategies that could allow clinically acceptable systems to emerge

Targeting danger molecules in tendinopathy: the HMGB1/TLR4 axis

Objectives: To seek evidence of the danger molecule, high-mobility group protein B1 (HMGB1) expression in human tendinopathy and thereafter, to explore mechanisms where HMGB1 may regulate inflammatory mediators and matrix regulation in human tendinopathy. Methods: Torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing ‘early pathology’) biopsies were collected from patients undergoing arthroscopic shoulder surgery. Control samples of subscapularis tendon were collected from patients undergoing arthroscopic stabilisation surgery. Markers of inflammation and HMGB1 were quantified by reverse transcriptase PCR (RT-PCR) and immunohistochemistry. Human tendon-derived primary cells were derived from hamstring tendon tissue obtained during hamstring tendon anterior cruciate ligament reconstruction and used through passage 3. In vitro effects of recombinant HMGB1 on tenocyte matrix and inflammatory potential were measured using quantitative RT-PCR, ELISA and immunohistochemistry staining. Results: Tendinopathic tissues demonstrated significantly increased levels of the danger molecule HMGB1 compared with control tissues with early tendinopathy tissue showing the greatest expression. The addition of recombinant human HMGB1 to tenocytes led to significant increase in expression of a number of inflammatory mediators, including interleukin 1 beta (IL-1β), IL-6, IL-33, CCL2 and CXCL12, in vitro. Further analysis demonstrated rhHMGB1 treatment resulted in increased expression of genes involved in matrix remodelling. Significant increases were observed in Col3, Tenascin-C and Decorin. Moreover, blocking HMGB1 signalling via toll-like receptor 4 (TLR4) silencing reversed these key inflammatory and matrix changes. Conclusion: HMGB1 is present in human tendinopathy and can regulate inflammatory cytokines and matrix changes. We propose HMGB1 as a mediator driving the inflammatory/matrix crosstalk and manipulation of the HMGB1/TLR4 axis may offer novel therapeutic approaches targeting inflammatory mechanisms in the management of human tendon disorders

Quality management systems in Aboriginal Community Controlled Health Services: a review of the literature

Background A national accreditation policy for the Australian primary healthcare (PHC) system was initiated in 2008. While certification standards are mandatory, little is known about their effects on the efficiency and sustainability of organisations, particularly in the Aboriginal Community Controlled Health Service (ACCHS) sector. Aim The literature review aims to answer the following: to what extent does the implementation of the International Organisation for Standardization 9001:2008 quality management system (QMS) facilitate efficiency and sustainability in the ACCHS sector? Methods Thematic analysis of peer-reviewed and grey literature was undertaken from Australia and New Zealand PHC sector with a focus on First Nations people. The databases searched included Medline, Scopus and three Informit sites (AHB-ATSIS, AEI-ATSIS and AGIS-ATSIS). The initial search strategy included quality improvement, continuous quality improvement, efficiency and sustainability. Results Sixteen included studies were assessed for quality using the McMaster criteria. The studies were ranked against the criteria of credibility, transferability, dependability and confirmability. Three central themes emerged: accreditation (n=4), quality improvement (n=9) and systems strengthening (n=3). The accreditation theme included effects on health service expenditure and clinical outcomes, consistency and validity of accreditation standards and linkages to clinical governance frameworks. The quality improvement theme included audit effectiveness and value for specific population health. The theme of systems strengthening included prerequisite systems and embedded clinical governance measures for innovative models of care. Conclusion The ACCHS sector warrants reliable evidence to understand the value of QMSs and enhancement tools, particularly given ACCHS (client-centric) services and their specialist status. Limited evidence exists for the value of standards on health system sustainability and efficiency in Australia. Despite a mandatory second certification standard, no studies reported on sustainability and efficiency of a QMS in PHC

Older adults’ experiences with using wearable devices:Qualitative systematic review and meta-synthesis

Background: Older adults may use wearable devices for various reasons, ranging from monitoring clinically relevant health metrics or detecting falls to monitoring physical activity. Little is known about how this population engages with wearable devices, and no qualitative synthesis exists to describe their shared experiences with long-term use. Objective: This study aims to synthesize qualitative studies of user experience after a multi-day trial with a wearable device to understand user experience and the factors that contribute to the acceptance and use of wearable devices. Methods: We conducted a systematic search in CINAHL, APA PsycINFO, PubMed, and Embase (2015-2020; English) with fixed search terms relating to older adults and wearable devices. A meta-synthesis methodology was used. We extracted themes from primary studies, identified key concepts, and applied reciprocal and refutational translation techniques; findings were synthesized into third-order interpretations, and finally, a “line-of-argument” was developed. Our overall goal was theory development, higher-level abstraction, and generalizability for making this group of qualitative findings more accessible. Results: In total, we reviewed 20 papers; 2 evaluated fall detection devices, 1 tested an ankle-worn step counter, and the remaining 17 tested activity trackers. The duration of wearing ranged from 3 days to 24 months. The views of 349 participants (age: range 51-94 years) were synthesized. Four key concepts were identified and outlined: motivation for device use, user characteristics (openness to engage and functional ability), integration into daily life, and device features. Motivation for device use is intrinsic and extrinsic, encompassing many aspects of the user experience, and appears to be as, if not more, important than the actual device features. To overcome usability barriers, an older adult must be motivated by the useful purpose of the device. A device that serves its intended purpose adds value to the user’s life. The user’s needs and the support structure around the device—aspects that are often overlooked—seem to play a crucial role in long-term adoption. Our “line-of-argument” model describes how motivation, ease of use, and device purpose determine whether a device is perceived to add value to the user’s life, which subsequently predicts whether the device will be integrated into the user’s life. Conclusions: The added value of a wearable device is the resulting balance of motivators (or lack thereof), device features (and their accuracy), ease of use, device purpose, and user experience. The added value contributes to the successful integration of the device into the daily life of the user. Useful device features alone do not lead to continued use. A support structure should be placed around the user to foster motivation, encourage peer engagement, and adapt to the user’s preferences

Evaluation of In Vitro Virulence Characteristics of the Genus Pandoraea in Lung Epithelial Cells

Pandoraea species are emerging opportunistic pathogens capable of causing chronic lung infections in cystic fibrosis patients. This study examined the interactions of 17 Pandoraea isolates from the five identified species (Pandoraea apista, Pandoraea norimbergensis, Pandoraea pulmonicula, Pandoraea sputorum and Pandoraea pnomenusa) plus two Pandoraea genomospecies isolates with lung epithelial cells and their ability to form biofilms in vitro. Only three isolates showed an ability to invade A549 lung epithelial cells, and only one isolate was able to form biofilms. In contrast, all isolates triggered a pronounced pro-inflammatory response, with elevation of both interleukin (IL)-6 (two- to 19-fold) and IL-8 (10- to 50-fold) above that observed for a control strain of Escherichia coli. This property is likely to be a major factor in the pathogenesis of the genus

Fibroblast activation and inflammation in frozen shoulder

Introduction: Frozen shoulder is a common, fibro-proliferative disease characterised by the insidious onset of pain and progressively restricted range of shoulder movement. Despite the prevalence of this disease, there is limited understanding of the molecular mechanisms underpinning the pathogenesis of this debilitating disease. Previous studies have identified increased myofibroblast differentiation and proliferation, immune cell influx and dysregulated cytokine production. We hypothesised that subpopulations within the fibroblast compartment may take on an activated phenotype, thus initiating the inflammatory processes observed in frozen shoulder. Therefore, we sought to evaluate the presence and possible pathogenic role of known stromal activation proteins in Frozen shoulder, Methods: Shoulder capsule samples were collected from 10 patients with idiopathic frozen shoulder and 10 patients undergoing shoulder stabilisation surgery. Fibroblast activation marker expression (CD248, CD146, VCAM and PDPN, FAP) was quantified using immunohistochemistry. Control and diseased fibroblasts were cultured for in vitro studies from capsule biopsies from instability and frozen shoulder surgeries, respectively. The inflammatory profile and effects of IL-1β upon diseased and control fibroblasts was assessed using ELISA, immunohistochemistry and qPCR. Results: Immunohistochemistry demonstrated increased expression of fibroblast activation markers CD248, CD146, VCAM and PDPN in the frozen shoulder group compared with control (p < 0.05). Fibroblasts cultured from diseased capsule produced elevated levels of inflammatory protein (IL-6, IL-8 & CCL-20) in comparison to control fibroblasts. Exposing control fibroblasts to an inflammatory stimuli, (IL-1ß) significantly increased stromal activation marker transcript and protein expression (CD248, PDPN and VCAM). Conclusions: These results show that fibroblasts have an activated phenotype in frozen shoulder and this is associated with inflammatory cytokine dysregulation. Furthermore, it supports the hypothesis that activated fibroblasts may be involved in regulating the inflammatory and fibrotic processes involved in this disease

Stromal ‘activation’ markers do not confer pathogenic activity in tendinopathy

Tendinopathy is a highly prevalent musculoskeletal pathology associated with incremental injury as result of repetitive microtrauma. We sought to explore the physiological significance of stromal “activation” signatures in a human model of tendinopathy. Torn supraspinatus tendon and matched intact subscapularis tendon biopsies were collected from patients undergoing shoulder surgery while healthy tendon was collected from patients undergoing anterior cruciate ligament (ACL) reconstruction. Expression of stromal activation markers was analyzed at transcript/protein level using qRT‐PCR and immunohistochemistry. Gene expression of stromal activation markers was silenced by siRNA‐mediated knockdown or induced by IL‐1β stimulation. Expression of “activation” markers podoplanin, VCAM‐1 and CD248 was identified in human tendon tissue. Podoplanin and VCAM‐1 expression were significantly increased in tendinopathic tissue. Knockdown of podoplanin and VCAM‐1 in normal and tendinopathic tenocytes did not have any significant effect on expression of matrix genes COL1A1, COL3A1, TNC, or DCN. Similarly, no changes in release of inflammatory mediators IL‐6, IL‐8, and CCL2 were observed in podoplanin/VCAM‐1 knockdown cultures. Our data suggest that silencing expression of stromal “activation” markers does not affect the intrinsic inflammatory profile or matrix regulatory behavior of tenocytes. We propose that the term “activation” is more appropriately reflected by alterations in tenocyte behavior that induce changes in the stromal microenvironment and overall tissue architecture rather than identification through potentially arbitrary phenotypic traits

HLA-B*27:05 alters immunodominance hierarchy of universal influenza-specific CD8+ T cells

Seasonal influenza virus infections cause 290,000–650,000 deaths annually and severe morbidity in 3–5 million people. CD8+ T-cell responses towards virus-derived peptide/human leukocyte antigen (HLA) complexes provide the broadest cross-reactive immunity against human influenza viruses. Several universally-conserved CD8+ T-cell specificities that elicit prominent responses against human influenza A viruses (IAVs) have been identified. These include HLA-A*02:01-M158-66 (A2/M158), HLA-A*03:01-NP265-273, HLA-B*08:01-NP225-233, HLA-B*18:01-NP219-226, HLA-B*27:05-NP383-391 and HLA-B*57:01-NP199-207. The immunodominance hierarchies across these universal CD8+ T-cell epitopes were however unknown. Here, we probed immunodominance status of influenza-specific universal CD8+ T-cells in HLA-I heterozygote individuals expressing two or more universal HLAs for IAV. We found that while CD8+ T-cell responses directed towards A2/M158 were generally immunodominant, A2/M158+CD8+ T-cells were markedly diminished (subdominant) in HLA-A*02:01/B*27:05-expressing donors following ex vivo and in vitro analyses. A2/M158+CD8+ T-cells in non-HLA-B*27:05 individuals were immunodominant, contained optimal public TRBV19/TRAV27 TCRαβ clonotypes and displayed highly polyfunctional and proliferative capacity, while A2/M158+CD8+ T cells in HLA-B*27:05-expressing donors were subdominant, with largely distinct TCRαβ clonotypes and consequently markedly reduced avidity, proliferative and polyfunctional efficacy. Our data illustrate altered immunodominance patterns and immunodomination within human influenza-specific CD8+ T-cells. Accordingly, our work highlights the importance of understanding immunodominance hierarchies within individual donors across a spectrum of prominent virus-specific CD8+ T-cell specificities prior to designing T cell-directed vaccines and immunotherapies, for influenza and other infectious diseases